Underivatized, aqueous soluble β(1,3)-glucan (also known as PGG-glucan, triple helix-glucan (TH-glucan) or Betafectin®) is a novel and unique soluble β-glucan manufactured through a proprietary process. The biological activity of this molecule is clearly distinguishable from particulate or other soluble β-glucans. Numerous laboratories have reported direct induction of arachidonic acid metabolites (Czop et al., J. Immunol., 141(9):3170-3176 (1988)), cytokines (Abel and Czop, Intl. J. Immunopharmacol., 14(8):1363-1373 (1992); Doita et al., J, Leuk. Biol., 14(2):173-183 (1991)) and oxidative burst (Cain et al., Complement, 4:75-86 (1987); Gallin et al., Int. J. Immunopharmacol., 14(2):173-183 (1992)) by both particulate and soluble forms of β-glucans. In contrast, underivatized, aqueous soluble β(1,3)-glucan does not directly activate leukocyte functions such as oxidative burst activity (Mackin et al., FASEB J., 8:A216 (1994)), cytokine secretion (Putsiaka et al., Blood, 82:3695-3700 (1993)) or proliferation (Wakshull et al., J. Cell. Biochem. suppl., 18A:22 (1994)). Instead, underivatized, aqueous soluble β(1,3)-glucan primes cells for activation by secondary stimuli (Mackin et al. (1994); Brunke-Reese and Mackin, FASEB J. 8:A488 (1994); and Wakshull et al. (1994)).
The biological activity of β-glucans is mediated through specific receptors located on target cells. Several groups of investigators have described receptors which bind to and mediate phagocytosis of particulate β-glucan preparations (e.g., zymosan-like particles; Goldman (Immunology, 63(2):319-324 (1988); Exp. Cell. Res., 174(2):481-490 (1988); Engstad and Robertsen, Dev. Comp. Immunol., 18(5):397-408 (1994); Muller et al., Res. Immunol., 145:267-275 (1994)); Czop, Advances in Immunol., 38:361,398 (1986)); and have partially characterized these receptors (Czop and Kay, J. Exp. Med., 173:1511-1520 (1991); Szabo et al., J. Biol. Chem., 270:2145-2151 (1995)). The leukocyte complement receptor 3 (CR3, also known as MAC 1 or CD11b/CD18) has been reported to bind both particulate and some soluble β-glucans, as well as other polysaccharides (Thornton et al., J. Immunol., 156:1235-1246 (1996)). A soluble aminated β-glucan preparation has been shown to bind to murine peritoneal macrophages (Konopski et al., Biochim. Biophys. Acta, 1221:61-65 (1994)), and a phosphorylated β-glucan derivative has been reported to bind to monocyte cell lines (Muller et al., J. Immunol., 156:3418-3425 (1996)).